• Adherence and population pharmacokinetic properties of amodiaquine when used for seasonal malaria chemoprevention in African children

      Ding, J; Coldiron, ME; Assao, B; Guindo, O; Blessborn, D; Winterberg, M; Grais, RF; Koscalova, A; Langendorf, C; Tarning, J (American Society for Clinical Pharmacology and Therapeutics, 2019-10-25)
      Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly‐observed ideal conditions (n=136), and the adherence of SMC at an implementation phase in children participating in a case‐control study to evaluate SMC effectiveness (n=869). Amodiaquine and desethylamodiaquine concentration‐time profiles were described simultaneously by two‐compartment and three‐compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65‐71% when the first dose of SMC was directly observed and 71‐73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case‐control children showed complete adherence (all doses taken) in less than 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.
    • Intermittent Preventive Treatment for Malaria Among Children in a Refugee Camp in Northern Uganda: Lessons Learned

      Coldiron, M; Lasry, E; Bouhenia, M; Das, D; Okui, P; Nyehangane, D; Mwanga, J; Langendorf, C; Elder, G; Salumu, L; et al. (BioMed Central, 2017-05-23)
      Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin-piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69-0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67-0.72 among children aged 5-14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42-1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9-16.4% (95% CI 12.6-19.3) during the intervention, with the highest prevalence among children aged 5-14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.
    • Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger

      Grais, RF; Laminou, IM; Woi-Messe, L; Makarimi, R; Bouriema, SH; Langendorf, C; Amambua-Ngwa, A; D'Alessandro, U; Guérin, PJ; Fandeur, T; et al. (BioMed Central, 2018-02-27)
      In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine-pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011-2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing.